Opioids (alternatively referred to as opioid agonists), are often used as analgesics for the regulation of perceived pain in a patient. Representative examples of opioids include oxycodone, morphine, hydrocodone, and codeine. Although opioids are effective at regulating perceived pain, there are some significant drawbacks to their use. Opioids, for example, are potentially physically and psychologically addictive to a patient if used repeatedly over an extended period of time. With respect to delayed release opioid dosage forms, there is an additional risk that individuals to whom they have been prescribed (and/or other individuals) will attempt to crush or grind the dosage forms to breach the structure(s) used to achieve delayed release, and then ingest the crushed or ground dosage forms to achieve the euphoria or “high” associated with relatively rapid uptake of the opioid.
One technique to reduce such abuse of opioid-containing dosage forms is to include an opioid antagonist. Opioid antagonists are drugs that serve to neutralize or block the euphoric or analgesic and overall physiological effect of an opioid agonist, for example, in individuals who have overdosed on an opioid agonist, or as a daily treatment drug in individuals who are addicted to an opioid agonist. It is thought that opioid antagonists act on and compete for the same receptor sites in the brain as opioid agonists, and thereby neutralize or block the resulting-analgesic or euphoric effects of the opioid agonist.
Various attempts have been made to reduce the risks of overdose on and addiction to opioid agonists. One approach has involved delivering both the opioid agonist and a suitable opioid antagonist in a single dosage form. For example, U.S. Publication No. 2004/0202717, the entirety of which is incorporated herein by reference, discloses opioid agonist dosage forms comprising inert beads that are coated, in turn, with an opioid antagonist and a polymer that controls release of the opioid agonist following oral ingestion but which releases the opioid antagonist upon breach when the dosage form is crushed or ground.
The use of traditional inert cores such as sugar non-pareils, microcrystalline cellulose beads, and wax beads as substrates to deliver pharmaceutically active agents has potential drawbacks. For example, water may diffuse drug loaded cores prepared using the sugar non-pareils or and microcrystalline cellulose beads, and cause an increase in osmotic pressure in the case of sugar non-pareils and swelling in the case of microcrystalline cellulose beads. In drug loaded cores bearing a coating to control release of the active agent, as water continues to diffuse into the core, the higher osmotic pressure or swelling could eventually rupture the coating and result in “dose dumping” of the active agent. Further, wax beads are temperature sensitive, which makes processing difficult, and it can be difficult to adhere a drug solution onto a wax bead. The pliable nature of wax beads generally makes them less effective for release of opioid antagonist if the dosage form is crushed or damaged; in fact, wax beads may actually aid in the opioid antagonist remaining sequestered.
Another drawback inherent in the use of inert cores to deliver active agents is that the presence of an inert material necessarily increases the size of the dosage form. Including inert beads at the core of a dosage form can also limit a formulator's ability to modify other components of the dosage form, such as the drug or the polymer coating. Accordingly, it would be highly desirable to provide an oral dosage form that is resistant to abuse but does not suffer from the drawbacks associated with the use of inert cores.